text: In 2010, researchers developed an applicable targeting therapy for hepatocellular carcinoma (HCC) in humans. The identification of CSN5, the fifth subunit of the COP9 signalosome complex found in early HCC, was used as a therapeutic target for siRNA induction. Systemic delivery of modified CSN5siRNA encapsulated in SNALPs significantly inhibited hepatic tumor growth in the Huh7-luc+ orthotopic xenograft model of human liver cancer. SiRNA-mediated CSN5 knockdown was also proven to inhibit cell-cycle progression and increases the rate of apoptosis in HCC cells in vitro. Not only do these results demonstrate the role of CSN5 in liver cancer progression, they also indicate that CSN5 has an essential role in HCC pathogenesis. In conclusion, SNALPs have been proven to significantly reduce hepatocellular carcinoma tumor growth in human Huh7-luc* cells through therapeutic silencing.